Lycorenine-type alkaloids

A definite picture of the biosynthesis of norpluviine (10), the key intermediate to the pyrrolophenanthridine, and the lycorenine-type alkaloids was derived from two sets of feeding experiments. 

Lycorenine-type alkaloids derived from [2]benzopyrano [3,4g]indole) including both lycorenine and homolycorine ... 

A comparison of the molecular rotations of lycorine and 2-epilycorine provided the first evidence for the absolute configuration of alkaloids of the lycorine type by the application of Mills rule. The development of suitable chemical methods of interconversion between the lycorine- and lycorenine-type alkaloids permitted an additional correlation between the two types by the Hudson-Klyne lactone rule. These assignments have recently been shown to be correct by X-ray crystallographic methods (65). With these findings the structure and absolute configuration of lycorine is described by I (R, Ri = H). The absolute configurations of many of the alkaloids discussed in Section III also are secure because these alkaloids have been interrelated and converted to known compounds of the lycorine series. 

Recent spectral data have shown that the alkaloid is best represented by LVII or its mirror image. Unlike hippeastrine which gives a single dihydro derivative upon catalytic reduction, candimine gives two isomeric dihydro compounds (mp 167° and 183°). Hydrogenation studies in both the lycorine- and lycorenine-type alkaloids have demonstrated... 

There is a close structural similarity between the alkaloids of the lycorine and lycorenine types. A hypothetical cleavage of XLV between nitrogen and C-7, followed by 180° rotation of the hexahydroindole... 

These alkaloids are among the most abundant of the bases derived from the [2]benzopyrano[3,4gf]indole nucleus in the Amaryllidaceae family, and the title of this section is derived from this fact. Lycorenine (LXVI) was one of the first Amaryllidaceae alkaloids to be studied and a summary of the chemical degradations leading to this structure (without stereochemical implications) has been given in Volumes II and VI. Lycorenine and the corresponding lactone, homolycorine (LXVII), not only serve as the reference alkaloids of the group for recent spectroscopic studies but also provides a chemical correlation with the lycorine-type alkaloids. Several important chemical interconversions are given below. 

The biosynthesis of lycorenine- and tazettine-type alkaloids cannot be accommodated within the concept of the phenyl-phenyl oxidative... 

The conversion of norpluviine 261 into homolycorine 3 has been validated via the benzylic oxidation at C6 position followed by B-ring opening to form an amino aldehyde with a free hydroxyl group, which gives alkaloid lycorenine 54 after 77,0-methylation [112]. Finally, a subsequent oxidation produces homolycorine 3 (Scheme 17.5). Recently, the transformation from lycorine-type skeleton into homolycorine-type alkaloid has been experimentally demonstrated through a total synthesis of alkaloid clivonine 76 [113]. 

Manas CG, Paddock VL, Bochet CG, Spivey AC, White AJP, Mann I, Oppolzer W (2010) Total synthesis of the lycorenine-type amaryllidaceae alkaloid (-H/-)-cliv(mme via a biomi-metic ring-switch from a lycorine-type progenitor. J Am Chem Soc 132 5176... 

Alkaloids of this series encompass all bases derived from the [2]benzo-pyrano[3,4gr]indole nucleus. Although homolycorine and lycorenine are moderately abundant, most of the alkaloids of this type occur either in very minor amounts in accessible plants or in large quantities in species that are difficult to obtain. 

The alkaloids of the lycorine and homolycorine groups are, on the whole, the most common alkaloids in this genus. Lycorine (1), galanthine (7), and pluviine (11) (lycorine type) and homolycorine (26) and lycorenine (35) (homolycorine type) are particularly frequent, lycorine being the most abundant. The presence of these alkaloids is very significant in the sections Narcissus (mainly lycorine type). Pseudonarcissi (mainly homolycorine type), and Tazettae of the wild species, and in the Divisions 1, 2, and 4 of cultivars. 

The biological conversion of protocatechuic aldehyde into lycorenine (35), which proceeds via (9-methylnorbelladine (87) and norpluviine (12), first involves a reduction of the aldehyde carbonyl, and afterward, in the generation of lycorenine (35), oxidation of this same carbon atom. The absolute stereochemistry of these processes has been elucidated in subsequent experiments (194), and the results show that hydrogen addition and removal take place on the re-face of the molecules concerned (195), the initially introdueed hydrogen being the one later removed (196). It is noteworthy that norpluviine (12), unlike pluviine (11), is converted in Narcissus King Alfred primarily to alkaloids of the homolycorine type. Benzylie... 

Synthesis of alkaloids of the first structural type [such as lycorine (8), norpluviine (9), lycorenine (10), and homolycorine (11)] in various daffodil varieties may occur as indicated (Fig. 33.4). Radioactively labeled norbellidine (5) is incorporated into norpluviine (9). 

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